Project Summary Cerebral palsy (CP) is the most common physical disability in early childhood causing serious motor and sensory impairments. About 30% of children with CP have congenital hemiplegia, resulting from periventricular white matter injury (PV-WMI), which impairs the use of one hand and disrupts bimanual co-ordination. Congenital hemiplegia has a profound effect on each child?s life and, thus, is of great importance to public health. Changes in brain organization often occur following PV-WMI varies depending on the timing, location, and extent of the injury, as well as the functional system involved. Understanding these changes is essential for the development of novel or improved neurological rehabilitation strategies. This R21 application is designed to identify abnormal functional and anatomical brain reorganization associated with hand function in young children (18-24 months) with congenital hemiplegia due to unilateral PV-WMI using an innovative multi- modal neuroimaging approach. Multi-modal neuroimaging studies are rare in children with CP, and are nearly non-existent in young children with CP. By capitalizing on recent advances in pediatric magnetoencephalography (MEG) and diffusion MRI based multi-tensor tractography (MTT), we propose to develop an innovative pediatric MEG-guided MTT technique to determine the brain function-structure relations in young children with congenital hemiplegia. For pediatric MEG, we will use the BabyMEG system, a pediatric MEG system with unique features designed specifically for children 0 to 3 years, which is available at Boston Children?s Hospital. We hypothesize that motor commands of the paretic hand in children with unilateral PV- WMI are generated in the contralesional hemisphere, while sensory feedback is processed in the ipsilesional hemisphere. To test our hypothesis, we plan to: (i) determine with pediatric MEG the functional maps of the primary motor cortex (M1) during active movements of the index finger, and of the primary somatosensory cortex (S1) during passive movements of the index finger and during tactile stimulation of the thumb, middle, and little fingers; (ii) determine the integrity of the corticospinal motor and thalamocortical sensory tracts using our MEG-guided MTT technique; and (iii) correlate the functional changes in the activation maps of M1 and S1, and the structural changes in the corticospinal motor and thalamocortical sensory tracts, with the hand motor performance assessed with the Assisting Hand Assessment test. Our study will provide detailed insights into the neuroplastic mechanisms involved in the reorganization of hand sensorimotor function following lesions to the developing human brain. Our research will have direct impact on the quality of life of children with congenital hemiplegia, as well as other forms of CP, because it has the potential to: (i) inform the development of neurorehabilitation strategies tailored to individual patients? measurements, (ii) facilitate the development of plasticity-promoting interventions for specific brain networks, and (iii) determine optimal therapy parameters and which patient populations will benefit from such treatments.